Synthesis 2015; 47(08): 1091-1100
DOI: 10.1055/s-0034-1379992
paper
© Georg Thieme Verlag Stuttgart · New York

Proximity- and Chelation-Induced SNAr 1,4-Aromatic ortho-Substitution of ortho-Methoxyphenyl 2-Alkyl Ketones

Gwendal Grelier
Department of Chemistry, Université de Montréal, Station Centre-Ville, C. P. 6128, Montréal, Quebec H3C 3J7, Canada   Email: stephen.hanessian@umontreal.ca
,
Etienne Chénard
Department of Chemistry, Université de Montréal, Station Centre-Ville, C. P. 6128, Montréal, Quebec H3C 3J7, Canada   Email: stephen.hanessian@umontreal.ca
,
Martin Büschleb
Department of Chemistry, Université de Montréal, Station Centre-Ville, C. P. 6128, Montréal, Quebec H3C 3J7, Canada   Email: stephen.hanessian@umontreal.ca
,
Stephen Hanessian*
Department of Chemistry, Université de Montréal, Station Centre-Ville, C. P. 6128, Montréal, Quebec H3C 3J7, Canada   Email: stephen.hanessian@umontreal.ca
› Author Affiliations
Further Information

Publication History

Received: 20 November 2014

Accepted after revision: 22 December 2014

Publication Date:
12 February 2015 (eFirst)

Abstract

The direct displacement of an o-methoxy group in o-methoxyaryl ketones with aryl, alkyl, and alkenyl Grignard reagents to provide a series of o-substituted ketones is described. Application of this reaction to the synthesis of a C-methyl analogue of a cyclooxygenase inhibitor is shown. The scope and limitations are discussed.

Supporting Information

 
  • References

  • 1 Chénard E, Hanessian S. Org. Lett. 2014; 16: 2668
  • 2 Fuson RC, Speck SB. J. Am. Chem. Soc. 1942; 64: 2446
  • 3 Fuson RC, Bottorff EM, Speck SB. J. Am. Chem. Soc. 1942; 64: 1450
    • 4a Fuson RC, Wassmundt FW. J. Am. Chem. Soc. 1956; 78: 5409
    • 4b Rice JE, Shih HC, Hussain N, LaVoie EJ. J. Org. Chem. 1987; 52: 849
    • 4c Rice JE, He ZM. J. Org. Chem. 1990; 55: 5490
    • 4d Hotta H, Suzuki T, Miyano S. Chem. Lett. 1990; 143
    • 4e Hattori T, Suzuki T, Miyano S. J. Chem. Soc., Chem. Commun. 1991; 1375
    • 4f Hattori T, Suzuki T, Hayashizaka N, Koike N, Miyano S. Bull. Chem. Soc. Jpn. 1993; 66: 3034
    • 4g Hattori T, Koike N, Miyano S. J. Chem. Soc., Perkin Trans. 1 1994; 2273
    • 4h Hattori T, Shimazumi Y, Goto H, Yamabe O, Morohashi N, Kawai W, Miyano S. J. Org. Chem. 2003; 68: 2099
    • 4i Parker JS, Smith NA, Welham MJ, Moss WO. Org. Process Res. Dev. 2004; 8: 45
    • 5a Meyers AI, Mihelich ED. J. Am. Chem. Soc. 1975; 97: 7383
    • 5b Meyers AI, Gabel R, Mihelich ED. J. Org. Chem. 1978; 43: 1372
    • 5c Meyers AI, Avila WB. J. Org. Chem. 1981; 46: 3881
    • 5d Meyers AI, Lutomski KA. Synthesis 1983; 105
    • 5e Meyers AI, Lutomski KA. J. Am. Chem. Soc. 1982; 104: 879
    • 5f Wilson JM, Cram DJ. J. Am. Chem. Soc. 1982; 104: 881
    • 5g Meyers AI, Flisak JR, Aitken RA. J. Am. Chem. Soc. 1987; 109: 5446
    • 5h Patten AD, Nguyen Nhan H, Danishefsky SJ. J. Org. Chem. 1988; 53: 1003
    • 5i Rizzacasa MA, Sargent MV. J. Chem. Soc, Chem. Commun. 1990; 894
    • 5j Meyers AI, Willemsen JJ. Tetrahedron 1998; 54: 10493
  • 6 Brockway AJ, Gonzalez-Lopez M, Fettinger JC, Shaw JT. J. Org. Chem. 2011; 76: 3515
  • 7 Jimenez-Oses G, Brockway AJ, Shaw JT, Houk KN. J. Am. Chem. Soc. 2013; 135: 6633
  • 9 Kim Y.-J, Brown SP, Cao Q, Dransfield PJ, Du X, Houze J, Jiao XY, Kohn TJ, Lai S, Li A.-R, Lin D, Luo J, Medina JC, Reagan JD, Pattaropong V, Schwarz M, Shen W, Su Y, Swaminath G, Vimolratana M, Wang X, Xiong Y, Yang L, Yu M, Zhang J, Zhu L. US Patent 48 527, 2009
  • 10 Shiozawa A, Narita K, Izumi G, Kurashige S, Sakitama K, Ishikawa M. Eur. J. Med. Chem. 1995; 30: 85
    • 11a Khanapure SP, Garvey DS, Earl RA, Ezawa M, Fang X, Gaston RD. US Patent 119 977, 2002
    • 11b Khanapure SP, Garvey DS, Young DV, Ezawa M, Earl RA, Gaston RD, Fang X, Murty M, Martino A, Shumway M, Trocha M, Marek P, Tam SW, Janero DR, Letts LG. J. Med. Chem. 2003; 46: 5484

      For some examples, see:
    • 12a Kuo Y.-H, Wu M.-D, Huang R.-L, Kuo L.-MY, Hsu Y.-W, Liaw C.-C, Hung C.-C, Shen Y.-C, Ong C.-W. Planta Med. 2005; 71: 646
    • 12b Gao X.-M, Pu J.-X, Huang S.-X, Yang L.-M, Huang H, Xiao W.-L, Zheng Y.-T, Sun H.-D. J. Nat. Prod. 2008; 71: 558
    • 12c Li X.-N, Pu J.-X, Du X, Yang L.-M, An H.-M, Lei C, He F, Luo X, Zheng Y.-T, Lu Y, Xiao W.-L, Sun H.-D. J. Nat. Prod. 2009; 72: 1133
    • 12d Yang G.-Y, Li Y.-K, Wang R.-R, Li X.-N, Xiao W.-L, Yang L.-M, Pu J.-X, Zheng Y.-T, Sun H.-D. J. Nat. Prod. 2010; 73: 915
    • 12e Yang J.-H, Zhang H.-Y, Wen J, Du X, Chen J.-H, Zhang H.-B, Xiao W.-L, Pu J.-X, Tang X.-C, Sun H.-D. J. Nat. Prod. 2011; 74: 1028
  • 13 Hanessian S, Chénard E. Org. Lett. 2012; 14: 3222
  • 14 See the experimental section.
  • 15 Friedel–Crafts acylation and alkylation of the potassium enolate with allyl iodide was used to prepare all of Grignard precursor 1.
  • 16 Result not shown; addition of LiCl (3 equiv) and increased temperature (reflux) did not change the outcome of the reaction.
  • 17 For a recent review, see: Sun C.-L, Shi Z.-J. Chem. Rev. 2014; 114: 9219

    • For examples, see:
    • 18a Ref. 7.
    • 18b Ref. 9.
    • 18c Kakiuchi F, Kan S, Igi K, Chatani N, Murai S. J. Am. Chem. Soc. 2003; 125: 1698
    • 18d Gandeepan P, Parthasarathy K, Cheng C.-H. J. Am. Chem. Soc. 2010; 132: 8569

    • For reviews, see:
    • 18e Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6723
    • 18f Suzuki A. J. Organomet. Chem. 1999; 576: 147
    • 18g Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457

      For reviews on decarboxylative Pd-catalyzed cross-couplings, see:
    • 19a Rodriguez N, Goossen LJ. Chem. Soc. Rev. 2011; 40: 5030
    • 19b Goossen LJ, Goossen K. Top. Organomet. Chem. 2013; 44: 121

    • For examples, see:
    • 19c Voutchkova A, Coplin A, Leadbeater NE, Crabtree RH. Chem. Commun. 2008; 6312
    • 19d Hu P, Shang Y, Su W. Angew. Chem. Int. Ed. 2012; 51: 5945